Throughout this application various publications are referred to in superscripts. Full citations for these references may be found at the end of the specification. The disclosures of these publications are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.
Atherosclerosis is an inflammatory disease of the arterial wall in which T cell- and other immune cell-mediated immunity play a significant component8,9. It is well known that atherosclerosis can lead to serious problems, including heart attack, stroke, or even death. Atherosclerosis can affect any artery in the body, such as arteries in the heart, brain, kidneys, legs, pelvis, and arms. As a consequence, different diseases can develop based on the arteries that are affected. More than 80 million Americans suffer from some form of cardiovascular disease including atherosclerosis10. Atherosclerosis related diseases include coronary heart disease (the number one killer of both men and women in the US), carotid artery disease, peripheral arterial disease and chronic kidney disease.
The B7 ligand family binds to the CD28 receptor family on T cells and other immune cells, which critically regulates functions of immune cells. The currently known members of the B7 family includes B7-1 (CD80), B7-2 (CD86), B7h (CD275), PD-L1 (B7-H1, CD274), PD-L2 (CD273), B7-H3 (CD276), B7x (B7-H4/B7s1) and HHLA2 (B7h7/B7-H5), whereas the CD28 family contains CD28, CTLA-4 (CD152), ICOS (CD278) and PD-1 (CD279)1,2. B7x is a member of the B7/CD28 families and inhibits T cell function3. B7x inhibits T cell functions through binding activated T cells and myeloid derived suppressor cells. Over-expression of B7x abrogates pancreas damage mediated by self-reactive CD4 and CD8 T cells in vivo4-7.
The present invention addresses the serious and long-felt need for improved methods for preventing and/or treating cardiovascular diseases such as atherosclerosis using B7x and B7x derivatives.